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Lesson Concepts

Acid-base regulation

  • pH defined, blood pH normally with a narrow range
  • Carbonic acid, bicarbonate buffer
  • Experiment: The effect of hyperventilation on pH
  • Experiment: Respiratory acidosis
  • Experiment: Respiratory alkalosis
  • Experiment: Metabolic acidosis
  • Experiment: Relationship between inspired CO2 and arterial bicarbonate
  • Acute respiratory acidosis: arterial pH & arterial HCO3-
  • Davenport acid-base diagram
  • Acute metabolic acidosis: interpret graph of arterial HCO3- versus arterial pH
  • Acute metabolic alkalosis: interpret graph of arterial HCO3- versus arterial pH

Baroreceptor reflex

  • Baroreceptor reflex, orthostatic hypotension (postural hypotension)
  • Experiment: Calculation of pulse pressure from systolic and diastolic pressures
  • Experiment continued: Calculation of MAP using formula (compare model value with calculated value)
  • Experiment continued: Measure heart rate
  • Experiment continued: Effect of lying to standing transition on cardiovascular system with baroreceptor reflex input intact
    • Carotid pressure, baroreceptor nerve activity, sympathetic nerve activity
  • Experiment: Effect of drug midodrine, a vasoconstrictor, on cardiovascular parameters
  • Experiment: orthostatic hypotension (Task: find a good way to recreate the disease in the simulation)
  • Treating orthostatic hypotension (Task: Try 3 different treatments to find the one that works best)

Control of blood flow

  • Cardiac output (CO = SV × HR)
  • Experiment: Effect of exercise on cardiovascular output (CO)
  • Experiment continued: Baseline CO
  • Experiment continued: Basal metabolism
  • In practice, metabolism is often measured by recording the rate of O2 consumption
  • Experiment continued: Increase in metabolism with exercise
  • Metabolic scope defined
  • Experiment continued: Skeletal muscle blood flow during exercise
  • Experiment continued: Increased cardiac output during exercise
    • During exercise, heart rate and stroke volume both increased, contributing to the increase in cardiac output.
  • Experiment: measure CO, HR, and SV during exercise
  • Experiment: Do a linear regression in Excel with data exported from Just Physiology.
  • Total peripheral resistance
  • CO = (MAP – PRA)/TPR; where PRA is the mean pressure in the right atrium.
  • The increase in CO during exercise is largely due to a decrease in TPR.
  • The body controls MAP by regulating CO and TPR.
  • Decrease in TPR due to increase in blood vessel diameter
  • Experiment: Measure change in blood flow to muscle, bone, kidneys, brain, skin, and GI tract from resting state to exercising state.
    • Some organs decrease their blood flow during exercise, others increase their blood flow.
  • Local control of blood vessel dilation
  • The ANS shunts some blood flow away from specific vascular beds during exercise
  • An increase in blood flow to the skin helps to dissipate heat.

Control of ventilation

  • Tidal ventilation
  • Conducting zone and respiratory zone
  • Diaphragm
  • Inspiration
  • Expiration
  • Total lung capacity
  • Tidal volume
  • Dead space
  • Calculate: Alveolar volume = volume of lung at end of inspiration – dead space
  • Calculate: Alveolar volume exchanged per breath
  • Functional residual capacity defined
  • Inspiratory reserve capacity defined
  • Vital capacity defined
  • Forced expiratory volume defined
  • FEV1 / FVC; Calculate the percentage given data.
  • Experiment: Control of tidal volume during exercise
  • Experiment continued: Control of ventilatory rate during exercise
  • Calculate alveolar ventilation [Alveolar Ventilation = (Tidal Volume - Dead Space) x (Respiratory Rate)]
  • Calculate the ratio of dead space volume to tidal volume during rest and during exercise.
  • The respiratory center in the brainstem
  • Central & Peripheral chemoreceptors
  • The relationship between inspired PO2 and total ventilation
  • The relationship between inspired PCO2 and total ventilation

Homeostasis 1: ANS

  • Intro to the autonomic nervous system (ANS)
  • The “fight-or-flight response” and the “rest and digest” response
  • The sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS)
  • Blood pressure is an important determinant of tissue perfusion.
  • Positive versus negative feedback
  • Mean arterial pressure (MAP) defined
  • Experiment: SNS and PNS inputs affect MAP
  • Experiment: Effect of Hemorrhage on blood pressure
  • Experiment: Hemorrhage challenge (Keep patient alive by monitoring and altering SNS and PNS input.)
  • Experiment: Positive correlation between SNS activity and heart rate
  • Experiment continued: Negative correlation between PNS activity and heart rate
  • Correlation does not prove that the autonomic nervous system controls heart rate.
  • Experiment: Manipulate SNS and PNS activity by clamping them to different levels. Observe the resulting changes in heart rate.
  • Choose the correct block diagram showing inputs that influence heart rate.

Homeostasis 2: Cardiovascular center

  • This lesson follows “Homeostasis 1: ANS Control of Heart Rate”.
  • The autonomic nervous system (review diagram and text).
  • SNS affects stroke volume and heart rate; PNS affects only heart rate.
  • Increases in stroke volume and/or heart rate lead to an increase in blood pressure and tissue perfusion
  • Experiment: The effects of SNS and PNS activity on blood pressure.
  • Experiment: Compensatory responses of the SNS and PNS
    • (decrease one branch of the ANS without clamping the other).
  • Experiment: Test the hypothesis that a 50% decrease in SNS activity is normally compensated for by an decrease in PNS activity due to the drop in blood pressure.
  • Cardiovascular center: identify the relationship between blood pressure and neural activity in the cardiovascular center on block diagram.
  • Feedback to the PNS and SNS from the cardiovascular center, which receives input from baroreceptors, prevents a sudden decrease in SNS activity from having a lasting effect on blood pressure.

Homeostasis 3: Baroreceptors

  • This lesson follows “Homeostasis 2: Cardiovascular center”.
  • Baroreceptors are described.
  • Baroreceptor locations
  • Block diagram shown that now includes the baroreceptors.
  • Experiment: In response to a decrease in carotid sinus pressure baroceptor activity decreases. In turn, SNS activity increases. Vagal firing decreases. Heart rate increases.
  • Students are asked to predict the relationship between arterial pressure and baroreceptor activity.
  • Experiment: Generate baroreceptor response curves
  • Experiment: Baroreceptor adaptation simulation
  • Baroreceptor adaptation possible link to hypertension

Homeostasis 4: Chemoreceptors

  • This lesson follows “Homeostasis 3: Baroreceptors”.
  • Central and peripheral chemoreceptors are described
  • CO2 + H2O ⇋ H+ + HCO3-
  • Change in [H+] in response to an increase in CO2
  • The effect of an increase in tissue perfusion on tissue PO2, PCO2, H+
  • Experiment: O2-chemoreceptor
    • Alter the O2 percentage of inhaled gas; measure the O2 chemoreceptor activity.
  • Experiment continued: Plot O2 chemoreceptor activity versus arterial PO2
  • Experiment continued: Plot SNS activity versus arterial PO2 and PNS activity versus arterial PO2
  • Experiment continued: Plot SNS activity versus O2 chemoreceptor activity
  • O2-chemoreceptor transduction
  • Experiment: CO2-chemoreceptor
  • Experiment continued: Plot chemoreceptor activity versus arterial PCO2
  • CO2-chemoreceptor transduction
  • The blood-brain barrier: How does a change in blood PCO2 affect central chemoreceptors, which are behind the blood-brain barrier?

Gas Exchange

  • Atmospheric gases
  • Calculate partial pressure
  • Calculate partial pressure, accounting for water vapor
  • Calculate partial pressure, accounting for altitude and water vapor
  • Basal metabolism (O2 consumption as a good proxy measure of aerobic metabolism)
  • Experiment: Respiratory exchange ratio
  • Fick’s 1st law of diffusion
  • Gas diffusion
  • Alveoli
  • Maximizing gas diffusion
  • Zones of the mammalian lung
    • The conducting zone
    • The respiratory zone
  • Dead space
  • Experiment: Changes in gas composition between inspired and alveolar gas
  • Experiment continued: Alveolar gas exchange
  • Experiment continued: Venous shunt
  • Experiment continued: CO2 exchange
  • Experiment continued: A paradox in O2 and CO2 capacities
  • Dissolved CO2 in Blood; Henry’s Law
  • CO2 transport as bicarbonate
    • CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
  • Carbonic anhydrase
  • O2 transport
    • Hemoglobin
  • Calculate number of moles of O2 per liter of blood.
  • The O2 dissociation curve.
  • Percent saturation
  • The P50 indicates affinity
  • Increased P50 indicates decreased affinity
  • Venous Blood has a decreased O2 affinity
  • O2 saturation of blood returning from the body
  • The difference between PO2 and PO2 concentration in the blood
  • Experiment: Effects of exercise on gas exchange
  • Changes in blood PO2 with moderate exercise: Decrease in pulmonary artery PO2
  • Cardiac output
  • The Fick Principle
  • The Fick Principle and cardiac output
  • Arteriovenous oxygen difference
  • Calculation of cardiac output
  • Hemoglobin affinity and exercise (Bohr Effect)
  • Shift in the O2-dissociation curve
  • Experiment: Effect of Altitude on O2 delivery to tissues
    • Rapid ascent
  • Experiment continued: The relationship between arterial O2 concentration and inspired PO2.
  • Decreased arterial PCO2 at altitude (Bohr Effect, left-ward shift in O2-dissociation curve)
  • Short-term changes in hematocrit are due to the movement of water between fluid compartments of the body.
  • The CO2—bicarbonate reaction
  • Respiratory alkalosis at high altitude due to increased ventilation

Glucose homeostasis: short-term

  • Intake of fuel and nutrients
  • Blood glucose
  • Experiment: Fast
    • Measure plasma [glucose], basal metabolic rate
  • Experiment continued: insulin and glucagon response to fast (decrease in blood glucose)
  • Experiment continued: Find the correlations between Insulin concentration and plasma [glucose], and glucagon concentration and plasma [glucose].
  • Experiment: The glucose tolerance test
  • Where did the infused glucose go?
    • Plot liver glycogen storage, muscle glycogen storage, total lipid stores, cellular protein
  • Glucose homeostasis: Type 1 diabetes
  • Experiment: Fasting with type 1 diabetes mellitus
  • Glucagon release
  • Experiment: Glucose tolerance test in subject with type 1 DM
  • Metabolic energy sources during starvation

Glucose homeostasis: long-term

  • This lesson follows “Glucose homeostasis: short-term”.
  • Metabolic energy sources
  • Experiment: long-term starvation (simulation of starvation for 5 days)
    • Energy stores: glycogen, adipose tissue lipids, and cell protein
  • Experiment continued: Insulin response to starvation
  • Daily Insulin fluctuations
  • Experiment continued: Glycogen metabolism during starvation
  • Gluconeogenesis
  • Basal metabolism
  • Experiment continued: lipid and protein catabolism
  • Ketoacidosis
  • Experiment: Lipid metabolism in type 1 diabetes mellitus
  • Experiment: measure blood ketoacid concentration.
  • Diabetic ketoacidosis
  • Experiment: Treating a patient with diabetic ketoacidosis

Physiological integration

  • This lesson follows “Control of Blood Flow”
  • Cardiac output (CO), Mean arterial pressure (MAP)
    • CO = HR × SV; MAP = CO × TPR
  • Heart rate regulation by the autonomic nervous system
  • The regulation of total peripheral resistance (TPR) by:
    • local control of the diameter of arterioles
    • central regulation by the sympathetic nervous system
  • The cardiovascular center
  • Integrating HR, SV, CO, and TPR; Block diagram
  • Large block diagram with many blanks. As progress is made the blanks will be filled in.
  • Experiment: Hemorrhage
    • Plot change in MAP after 1000 mL of blood loss
    • Plot change in cardiac output
  • Experiment continued: plot changes in HR, SV, and TPR after hemorrhage
  • Distinguish between direct effects of the hemorrhage versus compensatory responses
  • Determine how TPR and HR help to maintain MAP during hemorrhage.
  • Arteriole tone and TRP
  • TPR response to hemorrhage
  • Calculate the change in the blood vessel radius necessary to alter TPR by a certain amount using Poiseuille’s law
  • Selectivity of the vascular response
  • SV depends on End-diastolic volume (EDV) and end-systolic volume (ESV)
  • SV = (EDV - ESV)
  • EDV depends on venous return
  • Determine what factor leads to a decrease in EDV during hemorrhage
  • Capacitance and venous pressure
  • Venous tone
  • Skeletal-muscle pump
  • Respiratory pump
  • Effects propagating from the right to left side of the heart
  • Linking SNSA to ESV
  • Determine Factors affecting ESV
  • Heart contractility
  • Calculate ejection fraction (SV/EDV)
  • Sensory inputs to the cardiovascular system
  • Baroreceptors
  • Experiment: Regulation of conductance during hemorrhage
    • Arrange a number of tissue beds in order of percent decrease in conductance
  • Sending blood to the most sensitive tissues
  • Blood distribution in the vascular system
  • Experiment: Regulation of blood distribution
    • Find the percent change in volume of different parts of the circulatory system.
  • Veins and venules as blood reservoirs
    • A change in venous capacitance can transfer blood to other parts of the circulatory system.
  • Getting blood to the brain
  • Testing for orthostatic changes
  • Experiment: Postural adjustments
    • The hemorrhage subject is forced into a standing posture.
  • Experiment: Blood volume recovery
    • Short-term and long-term recovery
  • Components of blood
  • Hematocrit
  • Regulating GFR, water loss, and electrolyte loss
  • Regulation of renin release
  • Renin-angiotensin-aldosterone system
  • Osmoreceptors
  • Baroreceptor control of ADH release
  • Regulation of ECF volume and osmolarity
  • SNS control of the RAAS
  • Recovery: 24 h, Long-term
  • Dilution of the blood
  • The importance of tissue perfusion
  • Secretion of erythropoietin
  • Feedback control of erythropoietin release
  • Complete recovery (all banks in block diagram are filled in)

Pressure-flow 1: Introduction

  • Resistance
  • Hydrostatic pressure
  • Flow = pressure / resistance
  • Simple cardiovascular model.
  • Cardiac output is the blood flow
  • Rearrange the flow equation to solve for pressure
    • Blood Pressure = Cardiac Output × Vascular Resistance
  • How can cardiac output compensate for a change in vascular resistance?
  • (No simulation in this lesson)

Pressure-flow 2: Regulation

  • Organization of the autonomic nervous system (diagram)
  • Blood pressure and feedback
  • Experiment: Autonomic regulation of mean arterial pressure (MAP)
    • Determine how SNS and vagal inputs affect MAP
  • Pressure and resistance during exercise
  • A decrease in resistance allows for an increase in flow though the vascular bed of specific tissues
  • Experiment: Effect of exercise on MAP
  • Regulation of MAP during exercise
    • SNS rate and vagal rate
  • Experiment continued: Determine how MAP in maintained in a normal range during exercise.
    • Manipulate SNS activity and PNS activity; Plot cardiac output
  • Cardiac output = stroke volume × Heart Rate
  • Experiment: Explore how SNS and vagal inputs affect stroke volume
  • Autonomic regulation of heart rate
    • Manipulate SNS activity and PNS activity; Plot heart rate
  • Feedback from MAP affects SNS and PNS activity

Pressure-flow 3: CV Circuit Model

  • Hydrostatic pressure
  • Flow and resistance
  • Ohm’s law
  • Resistors in parallel
  • Hagen-Poiseuille equation
  • Organization of the cardiovascular system
  • Electric circuit model of the systemic circulation
  • Driving pressure of the systemic circulation
  • Cardiac output, flow, and current
  • (No simulation in this lesson)

Receptor-Ligand Binding

  • Ligand defined
  • Hormones defined
  • Hormone receptors
  • Binding capacity
  • The dissociation constant, KD
  • Differential ligand-receptor affinity in the human body
  • (No simulation in this lesson)

Renin-Angiotensin system

  • RAS explained.
  • Renin, angiotensin II, aldosterone
  • Experiment: increased NaCl intake
  • Experiment: increased NaCl intake, while angiotensin II is kept at a fixed concentration of 12 pg/ml

Water and Solute Distribution

  • Total water, ICF, and ECF
  • Experiment: Determine the body water distribution between various fluid compartments of the body.
  • Experiment continued: Water as a percentage of total body mass
  • Experiment continued: ICF as a percentage of total body water
  • Water distribution in major compartments
  • Intravascular, extravascular, interstitial
  • Water distribution in special compartments
  • Osmolarity
  • Osmotic coefficient
  • Osmosis
  • Active osmoles
  • Water moves relatively freely between the fluid compartments of the body.
  • Experiment: Water infusion
    • Determine how the water becomes distributed in the fluid compartments of the body in the short-term (2 min).
    • Determine how the water becomes distributed in the fluid compartments of the body in the long-term (1 h).
  • Water follows osmotically active particles
  • Calculate the total number of osmoles of various ionic species in particular fluid compartments of the body.
  • Ionic composition of the fluid compartments
  • Ion pumps maintain the gradients
  • Physiological saline solution
  • Experiment: Saline infusion
  • Hypertonic saline solution
  • Experiment: Hyperosmotic infusion